This project seeks to identify a central factor driving aging in order to develop targeted interventions to delay the onset or even reverse aging-related pathologies. My preliminary data demonstrate caloric restriction (CR), a proven intervention for increasing lifespan stimulates endogenous production of hydrogen sulfide gas and this is necessary for the stress resistance benefits of CR. Here, we test age related decline of endogenous hydrogen sulfide production and if it is delayed by a specific and more clinically favorable form of dietary restriction, methionine restriction, as a means to increase metabolic fitness, stress resistance and longevity.

Public Health Relevance

This project seeks to identify a central factor driving aging in order to develop targeted interventions to delay the onset or even reverse aging-related pathologies. My preliminary data demonstrate caloric restriction (CR), a proven intervention for increasing lifespan, stimulates endogenous production of hydrogen sulfide gas and this is necessary for the stress resistance benefits of CR. Here, we test age related decline of endogenous hydrogen sulfide production and if it is delayed by a specific and more clinically favorable form of dietary restriction, methionine restriction, as a means to increase metabolic fitness, stress resistance and longevity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Career Transition Award (K99)
Project #
5K99AG050777-02
Application #
9125706
Study Section
Neuroscience of Aging Review Committee (NIA)
Program Officer
Fridell, Yih-Woei
Project Start
2015-08-15
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
Hine, Christopher; Kim, Hyo-Jeong; Zhu, Yan et al. (2017) Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production. Cell Metab 25:1320-1333.e5
Nikonorova, Inna A; Al-Baghdadi, Rana J T; Mirek, Emily T et al. (2017) Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice. J Biol Chem 292:6786-6798